The stimulation of a beta-cell by its cognate antigen triggers a series of proliferation and differentiation steps in the development of an antibody- secreting plasma cell. At the molecular level, two key processes can alter the functional antibody gene that encodes the beta-cell antibody heavy chain. Heavy chain genes can both undergo class switching and somatic hypermutation. We have found that a microinjected gamma heavy chain gene can also undergo isotype switching and somatic mutation in transgenic mice. We will analyze transgenic mice to determine the mechanisms that are involved in transgene isotype switching and the nucleotide sequences that are important in allowing the switching process. We will also analyze the cis-acting sequences that are important in directing the hypermutational mechanism to a heavy chain transgene and whether RNA transcription plays a role in the hypermutation process.